The low success rate in eradicating rectal cancer with preoperative radiation therapy (XRT) (45 Gy in 25 fractions over 35 days) may be improved with the use of combined modality therapy, specifically chemotherapy administered during XRT (chemoradiation). 5-Fluorouracil (5-FU) is: 1) the single most active chemotherapeutic agent for rectal cancer; 2) a cycle-specific agent (i.e. preferentially attacks proliferating cells); and 3) has been shown to be valuable when combined with XRT for rectal cancer. Our hypothesis is that 5-FU plus XRT (chemoradiation) will be more effective in tumors with a high proportion of proliferating cells than in those with a low initial proliferative fraction, and that the pre-treatment labeling indices (LI) will predict: for the extent of clinical and histopathologic response induced by chemoradiation.. Labeling indices will be measured following in vivo perfusion with bromodeoxyuridine (BrdUrd) using flow cytometric techniques and immunohistochemistry. Other methods of, determining proliferative fractions using nuclear antigens will also be evaluated. A corollary to our primary hypothesis is that failure of a tumor to respond to chemoradiation is likely to have, at least in part, a cell kinetic basis. In addition to the fraction of cells that are proliferating, their rates of proliferation (e duration of s-phase, potential doubling time) will be examined by flow cytometric determination of the progression of the BrdUrd-labeled cells. Such measurements, performed prior to chemoradiation and at surgery, will be used to determine whether the rate of cell proliferation or changes in kinetic properties during therapy are related to the lack of tumor response in certain cases. Finally the long-term local control of these tumors will be assessed. The value of the extent of response to preoperative chemoradiation and of cytokinetic parameters predicting local control will be evaluated.